Association between LTA, TNF and AGER polymorphisms and late diabetic complications
Several candidate genes on the short arm of chromosome 6 including the HLA locus, TNF, LTA and AGER could be associated with late diabetic complications. The aim of our study was therefore to explore whether polymorphisms (TNF -308 G-->A, LTA T60N C-->A and AGER -374 T-->A) in these genes a...
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| description | Several candidate genes on the short arm of chromosome 6 including the HLA locus, TNF, LTA and AGER could be associated with late diabetic complications. The aim of our study was therefore to explore whether polymorphisms (TNF -308 G-->A, LTA T60N C-->A and AGER -374 T-->A) in these genes alone or together (as haplotypes) increased the risk for diabetic complications.
The studied polymorphisms were genotyped in 742 type 1 and 2957 type 2 diabetic patients as well as in 206 non-diabetic control subjects. The Haploview program was used to analyze putative linkage disequilibrium between studied polymorphisms. The TNF, LTA and AGER polymorphisms were associated with the HLA-DQB1 risk genotypes. The AGER -374 A allele was more common in type 1 diabetic patients with than without diabetic nephropathy (31.2 vs. 28.4%, p = 0.007). In a logistic regression analysis, the LTA but not the AGER polymorphism was associated with diabetic nephropathy (OR 2.55[1.11-5.86], p = 0.03). The AGER -374 A allele was associated with increased risk of sight threatening retinopathy in type 2 diabetic patients (1.65[1.11-2.45], p = 0.01) and also with increased risk for macrovascular disease in type 1 diabetic patients (OR 2.05[1.19-3.54], p = 0.01), but with decreased risk for macrovascular disease in type 2 diabetic patients (OR 0.66[0.49-0.90], p = 0.009). The TNF A allele was associated with increased risk for macrovascular complications in type 2 (OR 1.53 [1.04-2.25], p = 0.03, but not in type 1 diabetic patients.
The association between diabetic complications and LTA, TNF and AGER polymorphisms is complex, with partly different alleles conferring susceptibility in type 1 and type 2 diabetic patients. We can not exclude the possibility that the genes are part of a large haplotype block that also includes HLA-DQB1 risk genotypes. |
| doi_str_mv | 10.1371/journal.pone.0002546 |
| format | Article |
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The studied polymorphisms were genotyped in 742 type 1 and 2957 type 2 diabetic patients as well as in 206 non-diabetic control subjects. The Haploview program was used to analyze putative linkage disequilibrium between studied polymorphisms. The TNF, LTA and AGER polymorphisms were associated with the HLA-DQB1 risk genotypes. The AGER -374 A allele was more common in type 1 diabetic patients with than without diabetic nephropathy (31.2 vs. 28.4%, p = 0.007). In a logistic regression analysis, the LTA but not the AGER polymorphism was associated with diabetic nephropathy (OR 2.55[1.11-5.86], p = 0.03). The AGER -374 A allele was associated with increased risk of sight threatening retinopathy in type 2 diabetic patients (1.65[1.11-2.45], p = 0.01) and also with increased risk for macrovascular disease in type 1 diabetic patients (OR 2.05[1.19-3.54], p = 0.01), but with decreased risk for macrovascular disease in type 2 diabetic patients (OR 0.66[0.49-0.90], p = 0.009). The TNF A allele was associated with increased risk for macrovascular complications in type 2 (OR 1.53 [1.04-2.25], p = 0.03, but not in type 1 diabetic patients.
The association between diabetic complications and LTA, TNF and AGER polymorphisms is complex, with partly different alleles conferring susceptibility in type 1 and type 2 diabetic patients. We can not exclude the possibility that the genes are part of a large haplotype block that also includes HLA-DQB1 risk genotypes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0002546</identifier><identifier>PMID: 18575614</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Alleles ; Analysis ; Atherosclerosis ; Bioinformatics ; Cardiac and Cardiovascular Systems ; Cardiovascular disease ; Cardiovascular Disorders ; Chromosome 6 ; Chromosomes, Human, Pair 6 ; Clinical Medicine ; Complications ; Complications and side effects ; Cytokines ; Diabetes ; Diabetes and Endocrinology/Type 1 Diabetes ; Diabetes and Endocrinology/Type 2 Diabetes ; Diabetes Complications - genetics ; Diabetes mellitus ; Diabetic nephropathies ; Diabetic nephropathy ; Diabetic retinopathy ; Diabetics ; Female ; Gene polymorphism ; Genes ; Genetic aspects ; Genetics and Genomics/Genetics of Disease ; Genomes ; Genotype ; Genotypes ; Haplotypes ; Health risks ; Heart attacks ; Histocompatibility antigen HLA ; HLA antigens ; Humans ; Inflammation ; Kardiologi ; Kinases ; Klinisk medicin ; Linkage disequilibrium ; Lymphotoxin-alpha - genetics ; Male ; Medical and Health Sciences ; Medical research ; Medicin och hälsovetenskap ; Middle Aged ; Nephrology/Chronic Kidney Disease ; Nephropathy ; Ophthalmology/Diabetic Retinopathy ; Patients ; Polymorphism ; Polymorphism, Genetic ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic - genetics ; Regression analysis ; Retinopathy ; Risk ; Studies ; TNF inhibitors ; Tumor necrosis factor ; Tumor Necrosis Factor-alpha - genetics ; Tumor necrosis factor-TNF</subject><ispartof>PloS one, 2008-06, Vol.3 (6), p.e2546-e2546</ispartof><rights>COPYRIGHT 2008 Public Library of Science</rights><rights>2008 Lindholm et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Lindholm et al. 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c828t-ec733ddbb59827b6178084d2cd30daf2fe0d73bfd9f3e5a2ee0488dfcca91bda3</citedby><cites>FETCH-LOGICAL-c828t-ec733ddbb59827b6178084d2cd30daf2fe0d73bfd9f3e5a2ee0488dfcca91bda3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2429972/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2429972/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18575614$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://lup.lub.lu.se/record/1168484$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><contributor>Zhang, Cuilin</contributor><creatorcontrib>Lindholm, Eero</creatorcontrib><creatorcontrib>Bakhtadze, Ekaterina</creatorcontrib><creatorcontrib>Cilio, Corrado</creatorcontrib><creatorcontrib>Agardh, Elisabet</creatorcontrib><creatorcontrib>Groop, Leif</creatorcontrib><creatorcontrib>Agardh, Carl-David</creatorcontrib><title>Association between LTA, TNF and AGER polymorphisms and late diabetic complications</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Several candidate genes on the short arm of chromosome 6 including the HLA locus, TNF, LTA and AGER could be associated with late diabetic complications. The aim of our study was therefore to explore whether polymorphisms (TNF -308 G-->A, LTA T60N C-->A and AGER -374 T-->A) in these genes alone or together (as haplotypes) increased the risk for diabetic complications.
The studied polymorphisms were genotyped in 742 type 1 and 2957 type 2 diabetic patients as well as in 206 non-diabetic control subjects. The Haploview program was used to analyze putative linkage disequilibrium between studied polymorphisms. The TNF, LTA and AGER polymorphisms were associated with the HLA-DQB1 risk genotypes. The AGER -374 A allele was more common in type 1 diabetic patients with than without diabetic nephropathy (31.2 vs. 28.4%, p = 0.007). In a logistic regression analysis, the LTA but not the AGER polymorphism was associated with diabetic nephropathy (OR 2.55[1.11-5.86], p = 0.03). The AGER -374 A allele was associated with increased risk of sight threatening retinopathy in type 2 diabetic patients (1.65[1.11-2.45], p = 0.01) and also with increased risk for macrovascular disease in type 1 diabetic patients (OR 2.05[1.19-3.54], p = 0.01), but with decreased risk for macrovascular disease in type 2 diabetic patients (OR 0.66[0.49-0.90], p = 0.009). The TNF A allele was associated with increased risk for macrovascular complications in type 2 (OR 1.53 [1.04-2.25], p = 0.03, but not in type 1 diabetic patients.
The association between diabetic complications and LTA, TNF and AGER polymorphisms is complex, with partly different alleles conferring susceptibility in type 1 and type 2 diabetic patients. We can not exclude the possibility that the genes are part of a large haplotype block that also includes HLA-DQB1 risk genotypes.</description><subject>Aged</subject><subject>Alleles</subject><subject>Analysis</subject><subject>Atherosclerosis</subject><subject>Bioinformatics</subject><subject>Cardiac and Cardiovascular Systems</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular Disorders</subject><subject>Chromosome 6</subject><subject>Chromosomes, Human, Pair 6</subject><subject>Clinical Medicine</subject><subject>Complications</subject><subject>Complications and side effects</subject><subject>Cytokines</subject><subject>Diabetes</subject><subject>Diabetes and Endocrinology/Type 1 Diabetes</subject><subject>Diabetes and Endocrinology/Type 2 Diabetes</subject><subject>Diabetes Complications - genetics</subject><subject>Diabetes mellitus</subject><subject>Diabetic nephropathies</subject><subject>Diabetic nephropathy</subject><subject>Diabetic retinopathy</subject><subject>Diabetics</subject><subject>Female</subject><subject>Gene polymorphism</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetics and Genomics/Genetics of Disease</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Haplotypes</subject><subject>Health risks</subject><subject>Heart attacks</subject><subject>Histocompatibility antigen HLA</subject><subject>HLA antigens</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Kardiologi</subject><subject>Kinases</subject><subject>Klinisk medicin</subject><subject>Linkage disequilibrium</subject><subject>Lymphotoxin-alpha - genetics</subject><subject>Male</subject><subject>Medical and Health Sciences</subject><subject>Medical research</subject><subject>Medicin och hälsovetenskap</subject><subject>Middle Aged</subject><subject>Nephrology/Chronic Kidney Disease</subject><subject>Nephropathy</subject><subject>Ophthalmology/Diabetic Retinopathy</subject><subject>Patients</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic</subject><subject>Receptor for Advanced Glycation End Products</subject><subject>Receptors, Immunologic - genetics</subject><subject>Regression analysis</subject><subject>Retinopathy</subject><subject>Risk</subject><subject>Studies</subject><subject>TNF inhibitors</subject><subject>Tumor necrosis factor</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Tumor necrosis 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between LTA, TNF and AGER polymorphisms and late diabetic complications</title><author>Lindholm, Eero ; Bakhtadze, Ekaterina ; Cilio, Corrado ; Agardh, Elisabet ; Groop, Leif ; Agardh, Carl-David</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c828t-ec733ddbb59827b6178084d2cd30daf2fe0d73bfd9f3e5a2ee0488dfcca91bda3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Aged</topic><topic>Alleles</topic><topic>Analysis</topic><topic>Atherosclerosis</topic><topic>Bioinformatics</topic><topic>Cardiac and Cardiovascular Systems</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular Disorders</topic><topic>Chromosome 6</topic><topic>Chromosomes, Human, Pair 6</topic><topic>Clinical Medicine</topic><topic>Complications</topic><topic>Complications and side effects</topic><topic>Cytokines</topic><topic>Diabetes</topic><topic>Diabetes and Endocrinology/Type 1 Diabetes</topic><topic>Diabetes and Endocrinology/Type 2 Diabetes</topic><topic>Diabetes Complications - genetics</topic><topic>Diabetes mellitus</topic><topic>Diabetic nephropathies</topic><topic>Diabetic nephropathy</topic><topic>Diabetic retinopathy</topic><topic>Diabetics</topic><topic>Female</topic><topic>Gene polymorphism</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetics and Genomics/Genetics of Disease</topic><topic>Genomes</topic><topic>Genotype</topic><topic>Genotypes</topic><topic>Haplotypes</topic><topic>Health risks</topic><topic>Heart attacks</topic><topic>Histocompatibility antigen HLA</topic><topic>HLA antigens</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Kardiologi</topic><topic>Kinases</topic><topic>Klinisk medicin</topic><topic>Linkage disequilibrium</topic><topic>Lymphotoxin-alpha - genetics</topic><topic>Male</topic><topic>Medical and Health Sciences</topic><topic>Medical research</topic><topic>Medicin och 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Ekaterina</au><au>Cilio, Corrado</au><au>Agardh, Elisabet</au><au>Groop, Leif</au><au>Agardh, Carl-David</au><au>Zhang, Cuilin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association between LTA, TNF and AGER polymorphisms and late diabetic complications</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2008-06-25</date><risdate>2008</risdate><volume>3</volume><issue>6</issue><spage>e2546</spage><epage>e2546</epage><pages>e2546-e2546</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Several candidate genes on the short arm of chromosome 6 including the HLA locus, TNF, LTA and AGER could be associated with late diabetic complications. The aim of our study was therefore to explore whether polymorphisms (TNF -308 G-->A, LTA T60N C-->A and AGER -374 T-->A) in these genes alone or together (as haplotypes) increased the risk for diabetic complications.
The studied polymorphisms were genotyped in 742 type 1 and 2957 type 2 diabetic patients as well as in 206 non-diabetic control subjects. The Haploview program was used to analyze putative linkage disequilibrium between studied polymorphisms. The TNF, LTA and AGER polymorphisms were associated with the HLA-DQB1 risk genotypes. The AGER -374 A allele was more common in type 1 diabetic patients with than without diabetic nephropathy (31.2 vs. 28.4%, p = 0.007). In a logistic regression analysis, the LTA but not the AGER polymorphism was associated with diabetic nephropathy (OR 2.55[1.11-5.86], p = 0.03). The AGER -374 A allele was associated with increased risk of sight threatening retinopathy in type 2 diabetic patients (1.65[1.11-2.45], p = 0.01) and also with increased risk for macrovascular disease in type 1 diabetic patients (OR 2.05[1.19-3.54], p = 0.01), but with decreased risk for macrovascular disease in type 2 diabetic patients (OR 0.66[0.49-0.90], p = 0.009). The TNF A allele was associated with increased risk for macrovascular complications in type 2 (OR 1.53 [1.04-2.25], p = 0.03, but not in type 1 diabetic patients.
The association between diabetic complications and LTA, TNF and AGER polymorphisms is complex, with partly different alleles conferring susceptibility in type 1 and type 2 diabetic patients. We can not exclude the possibility that the genes are part of a large haplotype block that also includes HLA-DQB1 risk genotypes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>18575614</pmid><doi>10.1371/journal.pone.0002546</doi><tpages>e2546</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2008-06, Vol.3 (6), p.e2546-e2546 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1312290435 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aged Alleles Analysis Atherosclerosis Bioinformatics Cardiac and Cardiovascular Systems Cardiovascular disease Cardiovascular Disorders Chromosome 6 Chromosomes, Human, Pair 6 Clinical Medicine Complications Complications and side effects Cytokines Diabetes Diabetes and Endocrinology/Type 1 Diabetes Diabetes and Endocrinology/Type 2 Diabetes Diabetes Complications - genetics Diabetes mellitus Diabetic nephropathies Diabetic nephropathy Diabetic retinopathy Diabetics Female Gene polymorphism Genes Genetic aspects Genetics and Genomics/Genetics of Disease Genomes Genotype Genotypes Haplotypes Health risks Heart attacks Histocompatibility antigen HLA HLA antigens Humans Inflammation Kardiologi Kinases Klinisk medicin Linkage disequilibrium Lymphotoxin-alpha - genetics Male Medical and Health Sciences Medical research Medicin och hälsovetenskap Middle Aged Nephrology/Chronic Kidney Disease Nephropathy Ophthalmology/Diabetic Retinopathy Patients Polymorphism Polymorphism, Genetic Receptor for Advanced Glycation End Products Receptors, Immunologic - genetics Regression analysis Retinopathy Risk Studies TNF inhibitors Tumor necrosis factor Tumor Necrosis Factor-alpha - genetics Tumor necrosis factor-TNF |
| title | Association between LTA, TNF and AGER polymorphisms and late diabetic complications |
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